Valerio Giannellini

Improving gas chromatographic determination of residual solvents in pharmaceuticals by the combined use of headspace solid-phase microextraction and isotopic dilution

Cyclohexane and toluene were gas chromatographically determined via headspace solid-phase microextraction both in ketoprofen drug substance and ketoprofen capsules by a procedure relying on isotopic dilution (ID), an analytical tool derived from mass spectrometry (MS). This approach, using an internal standard method, gave mean precision and accuracy (RSD 2.56%, 2.97% and bias 0.21%, -0.99% for cyclohexane and toluene, respectively) not obtainable by the more commonly used external standard ones in the presence of real sample matrices. Optimisation of the operative conditions was also supported by experimental design. More generally, the proposed method, exploiting ID without resort to the costly MS instrumentation, could be recommended whenever opportune deuterated analogues of the target analytes and GC capillary columns able to separate all the peaks involved are ready available on the market.

Complete assignment of the 1H and 13C NMR spectra of secoisolariciresinol diglucoside, a mammalian lignan precursor isolated from Linum usitatissimum

A convenient isolation and purification protocol for secoisolariciresinol diglucoside (1), a precursor of the biologically active mammalian lignans enterolactone and enterodiol, from flax seed is reported together with an extensive 1D‐ and 2D‐NMR study (GE‐HSQC, GE‐HMBC and NOESY) leading to its definitive characterization as 2,3‐bis[(4‐hydroxy‐3‐methoxyphenyl)methyl]‐1,4‐butanediyl bis‐[R‐(R*,R*)]‐β‐D‐glucopyranoside. Copyright

Development of a densitometric method for the determination of cephalexin as an alternative to the standard HPLC procedure

A HPTLC-densitometric method was developed in order to obtain a reliable procedure for routine analysis of cephalexin in pharmaceutical formulations. Optimization of TLC conditions for the densitometric scanning was reached by eluting HPTLC silica gel plates in an horizontal developing chamber. Quantitation of cephalexin was performed in single beam reflectance mode by using a computer-controlled densitometric scanner and applying a five-point calibration. A linear regression has been found in the 200-1000 ng range. The setup method is precise, reproducible and accurate. Recovery was also assessed by comparison with the HPLC USP XXIII alternate method. In this case HPTLC-densitometry appears worth of consideration as being relatively inexpensive and time-saving (up to 12 samples can be determined simultaneously in less than 15 min with a solvent consumption of about 15 ml). The results suggest that the proposed method may be used in place of HPLC for the routine quantitation of cephalexin in both pure and dosage forms.

Direct quantitation of antiseptic quaternary ammonium compounds by fast atom bombardment mass spectrometry

The medicinally important quaternary ammonium salts benzyldimethyltetradecylammonium chloride (BDTA), cetylpyridinium chloride and benzethonium chloride, all afford, under fast atom bombardment (FAB) mass spectrometric conditions, abundant and persistent [M-Cl]+ species usefully amenable to quantitative analysis with the aid of thioglycerol as a liquid FAB matrix. The use of BDTA as an internal standard allowed a direct, precise and accurate determination of cetylpyridinium and benzethonium chlorides, either as pure samples or in dosage forms, in the concentration range 0.05-2 mg/ml.

Structural and conformational study of two solvates of a fulgenic acid derivative

The X-ray structures of two solvates of a fulgenic acid derivative (1), which is an essential intermediate in the synthesis of compounds with possible cancer-protecting properties, have been determined. The compound is closely related to those forming the class of fulgides, which are characterised by remarkable optical properties, that probably owe their existence to extensive electronic conjugation allowed by planarity of large parts of the molecules, a feature shared by 1. A conformational study has been undertaken to investigate the conditions for the existence, or absence, of such geometrical features and to understand if possible intramolecular hydrogen bonds may play a structure-determining role. Computed energy barriers for rotations around three C–C bonds have shed light on the nature of conformational rearrangements operative for the equilibration detected on the NMR time scale. Intramolecular hydrogen bonds do not favour the planar arrangement of large moieties and are not found to be competitive with intermolecular hydrogen bonds.